BIOINOVAR-Biocatalysis, Bioproducts and Bioenergy, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil.
Neurofarba Department, Università degli Studi di Firenze, Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino (Florence), Italy.
Molecules. 2020 Nov 23;25(22):5483. doi: 10.3390/molecules25225483.
Chagas disease still has no effective treatment option for all of its phases despite being discovered more than 100 years ago. The development of commercial drugs has been stagnating since the 1960s, a fact that sheds light on the question of how drug discovery research has progressed and taken advantage of technological advances. Could it be that technological advances have not yet been sufficient to resolve this issue or is there a lack of protocol, validation and standardization of the data generated by different research teams? This work presents an overview of commercial drugs and those that have been evaluated in studies and clinical trials so far. A brief review is made of recent target-based and phenotypic studies based on the search for molecules with anti- action. It also discusses how proteochemometric (PCM) modeling and microcrystal electron diffraction (MicroED) can help in the case of the lack of a 3D protein structure; more specifically, carbonic anhydrase.
尽管查加斯病在 100 多年前就已被发现，但目前仍然没有针对其所有阶段的有效治疗方法。自 20 世纪 60 年代以来，商业药物的开发一直停滞不前，这一事实揭示了药物发现研究是如何进展并利用技术进步的。是否是因为技术进步还不足以解决这个问题，还是因为缺乏不同研究团队生成的数据的协议、验证和标准化？本工作概述了迄今为止已在研究和临床试验中评估的商业药物和那些药物。简要回顾了基于寻找具有抗作用的分子的最近基于靶标的和表型的研究。还讨论了在缺乏 3D 蛋白质结构的情况下，如何使用蛋白化学计量（PCM）建模和微晶体电子衍射（MicroED）来提供帮助；更具体地说，就是碳酸酐酶。
